French and Israeli Scientists Use Stem Cells to Study Schizophrenia
Thanks to a simple human hair, French and Israeli scientists have made a breakthrough in understanding schizophrenia. French researchers at INSERM (the French equivalent of the British Medical Research Council) and an Israeli team from the Haifa Technion, have developed a new stem cell model in order to gain a better understanding of schizophrenia.
This “reversion” of human hair to its stem cell origin has made it possible to preserve a possible imprint of genetic defects in schizophrenics. This might one day allow scientists to identify those who will develop, or be at risk for developing, the crippling mental illness.
Schizophrenia is a multifactoral mental illness that, among other things, alters the functioning of certain nerve cells and their mitochondrial activity. One of the predominant hypotheses suggests that the factors that trigger schizophrenia originate from a maternal disorder (such as stress or infection) in the first trimester of pregnancy, during the formation of the neuroectoderm, the embryonic tissue from which the brain and skin cells are derived.
To check these two hypotheses and develop a cell model capable of screening new medicational molecules, the researchers had the idea of converting cells from the hair of patients into induced pluri-potent cells or iPSCs (i.e. immature cells capable of producing any type of cell in the organism in the culture), then differentiating them into neurons.
The hypothesis was that cells from the hair would have the same neuroectodermal origin as the neurons and thus, any possible defects acquired during the course of the development of the neuroectoderm would be preserved.
For this purpose, cells from the hair of three schizophrenic patients and two healthy patients were reprogrammed into induced pluri-potent stem cells. “Hair was chosen due to the ease of sampling and because the follicular keratinocytes share a common origin with neurons,” explains Daniel Aberdam. This technique is far less traumatic than a skin biopsy performed under local anesthetic and traditionally used for producing iPSC.
Dr. Aberdam the lead French researcher on the project explains “Once we were in possession of these cells, we could study them and convert them into every different cell type in order to understand what was not working and where it wasn’t working.”
Once these stem cells had been obtained, researchers caused them to turn into nerve cells, some of which exhibited a greatly reduced capacity to terminate their differentiation, while others were unable to reach maturity.
The researchers also showed that dopamine sensitivity of the mitochondria is disrupted in schizophrenics, causing an altered respiratory function in some of the nerve cells.
This shows that the cell model, even though it cannot imitate the full complexity of the brain, reproduces certain defects observed in patient samples and could be used for screening therapeutic molecules in schizophrenia. The French and Israeli scientists hope that one day, they will be able to use this information to create new screening measures and treatment for the disorder.